I am often asked about my thoughts on mammography. There is controversy in terms of it’s use as a screening tool and when used, how often and at what age to begin screening. There is no doubt as a diagnostic tool—when a mass is found and needs to be evaluated, it is effective. The question is how effective is it as a screening tool with the goal of early cancer detection with the subsequent assumption of a resultant longer lifespan.
In October 2015 the Journal of the American Medical Association published a large meta analysis of research. This was not a new study, rather an analysis of existing research-a study of studies. It shows an association of mammography (MMG) with a decrease in breast cancer mortality. The decreases in mortality increase with the age of the women screened, the largest decrease of breast cancer related mortality is with women aged 60-69 (because breast cancer frequency increases as you get older). The article acknowledges the issues of over diagnosis but unfortunately notes there are no studies with reliable data on this, nor on the impact of treatment for the over diagnosed. So this very important variable is still unclear.
The analysis gave no conclusive recommendations on the interval of screening between 1 or 2 years.
So where does this leave me? I agree that MMG is a tool which increases breast cancer diagnosis, and saves lives. How many lives it saves versus how many women will have unnecessary mastectomies, lumpectomies, radiation, chemotherapy, and thus shortened life expectancy or quality of life? This is the unknown. Some evidence puts this as equal to the magnitude of women who benefit from MMG, while others put this way below. But clearly MMG has a larger impact on women in their 60’s than in their 50’s than in their 40’s.
So what is a woman to do? I continue to support the US Preventative Health Services Task Force recommendations of beginning screening at age 50 and continuing every 2 years until 75 to 80 depending on the health of the woman. Beginning screening in the 40’s will pick up more cancer but the incidence is low relative to the older groups, which makes the unknown over diagnosis rate statistically more probable. However if you are more comfortable with the risk of over than under diagnose then start earlier. Clearly MMGs save some lives, but at a cost. Following your gut is always a good thing, as there clearly is no strong evidence based recommendations which include all the factors involved. Such is so often the case in women’s healthcare.
Current recommendations for women with average risk of breast cancer from earliest starting year to latest:
American College OB/GYNs and American College of Radiologists: age 40 repeat annually.
American Cancer Society: age 45 every year then every other year after 55—unless the woman wants more frequent screening.
US preventative Services Health Task Force: 50 repeat every 2 years.
Below is a synopsis of the study’s findings. The italics are my comments, the remainder quotes from the study.
Breast Cancer Mortality
We assessed the quality of the evidence for an overall mortality reduction with mammographic screening to be HIGH, but there is greater uncertainty about the absolute magnitude of the association (judged of MODERATE quality). In particular, there is limited direct evidence on screening effectiveness available for the US population.
Women who have MMG have a mortality reduction, how much of that is directly related to MMG is unclear.
In the meta-analyses of RCTs (randomized controlled trials) that stratified by age. Screening women younger than 50 years was consistently associated with a statistically significant reduction in breast cancer mortality of approximately 15%. Screening women 50 years or older was associated with slightly greater mortality reduction (14%-23%), mostly related to a greater reduction in women 60 to 69 years (31%-32%). Data for women 70 to 74 years were limited to the Swedish Two-County trial, with differences in the direction of association variable based on methods for case classification. In other words—no data.
Although there was consistent evidence that mammographic screening among women older than 40 years was associated with reduced breast cancer mortality, there was inconsistency in the estimate of the magnitude of association, and we judged the overall quality of the evidence to be MODERATE. Because of the very limited data on the effectiveness of screening for women older than 70, we judged the quality of evidence to be LOW, although modeling studies suggested that there may be benefit for women with higher life expectancies because of lack of comorbid conditions.80,81
What is clear is that for women over 50 the mortality reduction is greater than 15% and the rate of decreased mortality increases with the age of screening until 70 at least.
This in my mind is the biggest risk issue of MMG. It refers to MMG diagnosed early invasive or in situ cancer (this term refers to pre cancerous changes) which if left alone would resolve. In other words, a woman has a MMG which leads to a cancer diagnosis, but in fact what was found would go away without treatment. If we wait until a cancer is large enough to feel, it is agreed that this is a cancer that would most likely lead to advanced disease and death (unless something else more quickly caused death—not uncommon in older women) if untreated.
A pooled analysis of 13 studies reporting 16 estimates of overdiagnosis from 7 European countries (the Netherlands, Italy, Norway, Sweden, Denmark, United Kingdom, and Spain) found crude estimates ranging from 0% to 54%. After adjustment for breast cancer risk and lead time (the time between a cancer detected by MMG versus a cancer you can find on exam), estimates were reduced to 1% to 10%.
The validity of these adjustments is unknown.
In addition, estimates were higher when the analysis was based on attendance at screening rather than invitation (attendance, women who had MMG invitation women referred for MMG). The increase in overdiagnosis estimates with the population analyzed were similar to the increase in mortality reduction.
When looking at the women who actually had MMG the overdiagnosis estimates were higher. This is a mathematical issue, you remove the referred for MMG but not getting one women from the denominator—the bottom of the equation.
TAKE AWAY: The rates of women diagnosed with breast cancer who in fact did not have a deadly cancer was similar to the number of women whose lives were extended due to early detection with MMG. BUT THESE ARE DIFFERENT WOMEN. That is an important piece of the puzzle, the women overdiagnosed were not the women who had extended lives. Some win, some lose.
Screening interval (how often to have MMG annual vs every 2 years)
We judged the quality of the evidence on the association of screening interval with outcome to be LOW—although the evidence was consistent for a greater relative reduction with more frequent screening, especially for younger women, it is indirect.
Given the high degree of uncertainty about estimating overdiagnosis, we judged the quality of evidence for a quantitative estimate to be LOW for the association between screening at different intervals and overdiagnosis.
We just do not know, perhaps there is more overdiagnosis with annual vs every 2 years, but not great evidence.
We did not identify any direct evidence on the association between mammographic screening and life expectancy, which would require following up all participants in an RCT or cohort study until death from any cause.
Because estimates of life expectancy gains from screening are by definition indirect and there is considerable uncertainty about the value of several parameters important for estimating these gains (in particular the magnitude of mortality reduction associated with screening at different ages and different intervals), we judged the quality of evidence for the magnitude of the association between screening and life expectancy to be LOW.
So while there is claim to breast cancer mortality reduction (reduction of death from breast cancer), there is no evidence that actual life in years is extended by having a MMG.
Clinical Beast exam
We did not identify any evidence that directly estimated the association between CBE and mortality using methods comparable to the mammography studies. There were also no direct estimates of any association between age, CBE, and breast cancer mortality. ( Thus it simply hasn’t been studies in depth)A Japanese cohort study of 3453 women who simultaneously underwent CBE, mammography, or ultrasound found lower false-positive rates with CBE (5%) compared with mammography (8%), but no cancer cases were diagnosed on the basis of CBE alone. There was some evidence of over diagnosis with CBE and mammography, not supported in all studies.
I am unimpressed with the data on CBE-clincal breast exam. Some studies show a correlation between over diagnosis and CBE. This makes sense in that an unexplained palpable mass is worked up even in the absence of MMG evidence of malignancy. Meaning that if it is not clearly a benign cyst, biopsies will be done. This is due to the fact that MMG can and does miss breast cancer. So not doing CBE would miss cancers not seen by MMG. I have seen this a number of times in my practice. Some breast cancers are not seen on MMG, cancers of the breast lobes (as opposed to the breast ducts) are more likely not to be visible on MMG, for example.
Among women of all ages at average risk of breast cancer, screening was associated with a reduction in breast cancer mortality of approximately 20%, although there was uncertainty about quantitative estimates of the association of different breast cancer screening strategies in the United States. These findings and the related uncertainty should be considered when making recommendations based on judgments about the balance of benefits and harms of breast cancer screening.
(So there is an average approximately 20% reduction in mortality but no clarity on the magnitude of overdiagnosis and overtreatment.)
Benefits and Harms of Breast Cancer Screening
This systematic review reports that among US women at average risk for breast cancer, mammographic screening is associated with reduction in breast cancer mortality, but the magnitude of the benefits and harms of different screening strategies remains uncertain.
Here is a copy of the study abstract
Benefits and Harms of Breast Cancer Screening A Systematic Review
Evan R. Myers, MD, MPH1,2; Patricia Moorman, PhD1,3; Jennifer M. Gierisch, PhD, MPH1,4,5; Laura J. Havrilesky, MD, MHSc1,2; Lars J. Grimm, MD6; Sujata Ghate, MD6; Brittany Davidson, MD2; Ranee Chatterjee Mongtomery, MD1,4; Matthew J. Crowley, MD1,4,5; Douglas C. McCrory, MD, MHSc1,4,5; Amy Kendrick, RN, MSN1; Gillian D. Sanders, PhD1,4
JAMA. 2015;314(15):1615-1634. doi:10.1001/jama.2015.13183.
Importance Patients need to consider both benefits and harms of breast cancer screening.
Objective To systematically synthesize available evidence on the association of mammographic screening and clinical breast examination (CBE) at different ages and intervals with breast cancer mortality, overdiagnosis, false-positive biopsy findings, life expectancy, and quality-adjusted life expectancy.
Evidence Review We searched PubMed (to March 6, 2014), CINAHL (to September 10, 2013), and PsycINFO (to September 10, 2013) for systematic reviews, randomized clinical trials (RCTs) (with no limit to publication date), and observational and modeling studies published after January 1, 2000, as well as systematic reviews of all study designs. Included studies (7 reviews, 10 RCTs, 72 observational, 1 modeling) provided evidence on the association between screening with mammography, CBE, or both and prespecified critical outcomes among women at average risk of breast cancer (no known genetic susceptibility, family history, previous breast neoplasia, or chest irradiation). We used summary estimates from existing reviews, supplemented by qualitative synthesis of studies not included in those reviews.
Findings Across all ages of women at average risk, pooled estimates of association between mammography screening and mortality reduction after 13 years of follow-up were similar for 3 meta-analyses of clinical trials (UK Independent Panel: relative risk [RR], 0.80 [95% CI, 0.73-0.89]; Canadian Task Force: RR, 0.82 [95% CI, 0.74-0.94]; Cochrane: RR, 0.81 [95% CI, 0.74-0.87]); were greater in a meta-analysis of cohort studies (RR, 0.75 [95% CI, 0.69 to 0.81]); and were comparable in a modeling study (CISNET; median RR equivalent among 7 models, 0.85 [range, 0.77-0.93]). Uncertainty remains about the magnitude of associated mortality reduction in the entire US population, among women 40 to 49 years, and with annual screening compared with biennial screening. There is uncertainty about the magnitude of overdiagnosis associated with different screening strategies, attributable in part to lack of consensus on methods of estimation and the importance of ductal carcinoma in situ in overdiagnosis. For women with a first mammography screening at age 40 years, estimated 10-year cumulative risk of a false-positive biopsy result was higher (7.0% [95% CI, 6.1%-7.8%]) for annual compared with biennial (4.8% [95% CI, 4.4%-5.2%]) screening. Although 10-year probabilities of false-positive biopsy results were similar for women beginning screening at age 50 years, indirect estimates of lifetime probability of false-positive results were lower. Evidence for the relationship between screening and life expectancy and quality-adjusted life expectancy was low in quality. There was no direct evidence for any additional mortality benefit associated with the addition of CBE to mammography, but observational evidence from the United States and Canada suggested an increase in false-positive findings compared with mammography alone, with both studies finding an estimated 55 additional false-positive findings per extra breast cancer detected with the addition of CBE.
Conclusions and Relevance For women of all ages at average risk, screening was associated with a reduction in breast cancer mortality of approximately 20%, although there was uncertainty about quantitative estimates of outcomes for different breast cancer screening strategies in the United States. These findings and the related uncertainty should be considered when making recommendations based on judgments about the balance of benefits and harms of breast cancer screening.